FIGURE 1.

Clinical characteristics of patients affected with pulmonary fibrosis. FVC: forced vital capacity; FEV₁: forced expiratory volume in 1 s; TLC: total lung capacity; CT: computed tomography. a) Pedigrees of all families with pulmonary fibrosis with subsequent genotype analyses. Arrows indicate the proband from each family. Circles: females; squares: males; white symbols: not included in the study; white symbols with genotype: unaffected; black symbols: pulmonary fibrosis affected; +: wild-type “C” allele of S100A3/wild-type sequence of S100A13; −: mutant “T” allele of S100A3 (c.229C>T)/4 bp deletion of S100A13 (c.238–241delATTG). b) CT scans at initial presentation of the three patients (F1:IV-1, IV-2 and IV-3) showing central traction bronchiectasis (long arrow). The distribution of fibrotic changes was peribronchovascular. The periphery of the lungs was spared. Global volume loss was seen with retracting subpleural fat in the lateral portions of the fissures (short arrows). c) CT scans late in the disease course of patient F1:IV-2: upper chest axial view (left), lower chest axial view (middle) and coronal view (right). There was progression of the peribronchovascular fibrotic changes and volume loss. Patches of ground-glass densities were randomly distributed. d, e) High-resolution CT scans of patients d) F2:IV-7 and e) F2:IV-8 showing central traction bronchiectasis (long arrows). The distribution of fibrotic changes is peribronchovascular and central. The periphery of the lungs was spared. Global volume loss is seen evident by retracting subplural fat in the lateral portions of the fissures (short arrows). f) Pulmonary function tests of five patients and family two members heterozygous for both the p.R77C and p.I80Gfs*13 variants in S100A3 and S100A13, respectively. g) Pathology of one affected patient (F1:IV-2): generalised interstitial inflammation with fibrosis. The inflammation mostly consists of lymphocytes in a background of moderate interstitial fibrosis. No advanced lung fibrosis with honeycombing is identified. No granulomas, microgranuloma or vasculitis are noted. Scale bar: left image 100 µm, other images 50 µm. h) Pathology of another affected patient (F2:IV-7): interstitial inflammation with fibrosis in a diffuse pattern with no temporal heterogeneity. Advanced fibrosis seems to be sparing the subpleural space. No granulomas, microgranuloma or vasculitis are noted. Extensive sampling did not reveal a usual interstitial pneumonia-like pattern. Scale bar: left image 100 µm, other images 50 µm.